In-Silico Araçlar Kullanılarak Otizmle İlişkili CDH8 ve CDH10 Genlerindeki SNP'lerin Değerlendirilmesi

Abstract

Otizm spektrum bozukluğu (OSB), yaygın ve çok faktörlü bir nörogelişimsel bozukluk (NB) olarak tanımlanır. Tekrarlayan davranış kalıplarının yanı sıra sosyal etkileşim ve iletişim bozukluğu belirtileri ile karakterizedir. Kadherin (CDH) süper ailesi, büyük bir sinaptik hücre adezyon molekülleri grubudur ve otizm de dahil olmak üzere NB ile geniş çapta ilişkilendirilmiştir. Bu çalışmanın amacı, otizm spektrum bozukluğu ile ilişkili ve amino asit değişikliklerine neden olan CDH8 ve CDH10 genlerinde potansiyel olarak zararlı olan missense tek nükleotid polimorfizmlerinin internet tabanlı yazılım araçları kullanılarak değerlendirilmesidir. Potansiyel olarak zararlı yanlış anlamlı SNP'leri tanımlamak için; tüm SNP'ler SIFT, PolyPhen-2, PROVEAN, SNPs&GO, Meta-SNP ve SNAP2 yazılım araçları kullanılarak tarandı ve ortak zararlı olanlar filtrelendi. Protein stabilizasyonu üzerindeki etkisi, I-Mutant 3.0 ve MUpro araçlarıyla araştırıldı. Bu ortak zararlı amino asit değişikliklerinin üç boyutlu modelleri HOPE yazılımı ile değerlendirildi. CDH8 genindeki 577 missense SNP'nin in silico analizi sonucunda; ‎SNP'ye zarar veren rs145143780 (Y572C) polimorfizmi tüm yazılım araçları tarafından tespit edilmiştir.‎ CDH10 geninde bulunan 526 missense SNP'nin in silico analiz sonuçlarına göre; rs13174039 (V459G), rs147882578 (N485K), rs201423740 (Y306C), rs201956238 (F317L) ve rs373340564 (R128C) ortak zarar veren SNP'ler, tüm polimorfizmlerde tüm yazılım araçları tarafından tanımlanmıştır. Bu çalışma sonucunda elde edilen verilerin gelecekte ilgili deneysel çalışmalara önemli katkılar sağlayacağı düşünülmektedir.

Keywords

• Tek nükleotid polimorfizmi
• CDH8
• CDH10
• in silico
• otizm spektrum bozukluğu (OSB)

Evaluation of SNP in the CDH8 and CDH10 Genes Associated with Autism Using In-Silico Tools

Abstract

Autism spectrum disorder (ASD) is defined as a pervasive and multifactorial neurodevelopmental disorder (ND). It is characterized by repetitive behavioral patterns as well as symptoms of social interaction and communication disorder. The cadherin (CDH) superfamily is a large group of synaptic cell adhesion molecules and has been widely related with ND, including autism. The aim of this study is to evaluate the potentially deleterious missense single nucleotide polymorphisms (SNPs) in CDH8 and CDH10 genes, which are related with ASD and cause amino acid changes, using internet-based software tools. To identify potentially harmful missense SNPs; all SNPs were screened using SIFT, PolyPhen-2, PROVEAN, SNPs&GO, Meta-SNP, and SNAP2 software tools, and common deleterious ones were filtered out. Its effect on protein stabilization was investigated with I-Mutant 3.0 and MUpro tools. Three-dimensional models of these common damaging amino acid changes were evaluated with the HOPE software. As a result of in silico analysis of 577 missense SNPs in the CDH8 gene; The rs145143780 (Y572C) polymorphism common damaging ‎SNP has been detected by all software tools.‎ According to the results of the in silico analysis of 526 missense SNPs found in the CDH10 gene; The rs13174039 (V459G), rs147882578 (N485K), rs201423740 (Y306C), rs201956238 (F317L) and rs373340564 (R128C) common damaging SNPs have been identified in all polymorphisms by all software tools. As a result of this study, it is thought that the data obtained will make important contributions to future relevant experimental studies.

Keywords

• Single nucleotide polymorphism (SNP)
• CDH8
• CDH10
• in silico
• autism spectrum disorder (ASD)

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